We propose to study the comparative enzymology of glyoxalase isolated from normal and abnormal tissue in order to examine the mechanism and regulation of the enzyme in different tissues and to test whether there are isozyme changes for glyoxalase in hosts bearing a neoplasia. This possible isozyme change may be of some diagnostic value in cancer detection, quite apart from the possibly important intracellular function of the enzyme. The basic methods for isolation, purification, and mechanism characterization of the enzymes have been worked out in previous studies, primarily using yeast and rat erythrocyte glyoxalase. Additional studies directed toward elucidating the metabolic functions of alpha-ketoaldehydes are proposed, with major emphasis placed upon determining the interrelationships between alpha-ketoaldehyde metabolism and glutathione metabolism. Studies on the broader role of glutathione in the detoxification of toxic and carcinogenic chemicals are planned, again with emphasis on the comparative enzymology of specific proteins in normal and abnormal tissues. The role of glutathione-transferases in the metabolism of polycyclic hydrocarbons will be examined in liver tissue with the aim of elucidating the relationship between tissue sensitivity to carcinogens and availability of glutathione for detoxification.